Immunomodulatory activity of dipeptidyl peptidase-4 inhibitors in immune-related diseases

Abstract

Dipeptidyl peptidase-4 (DPP-4), also known as CD26, is a 110-kDa cell surface glycoprotein with enzymatic and signal transducing activity. DPP-4/CD26 is expressed by various cells, including CD4+ and CD8+ T cells, B cells, dendritic cells, macrophages, and NK cells. DPP-4 inhibitors (DPP-4i) were introduced to clinics in 2006 as new oral antihyperglycemic drugs approved for type 2 diabetes mellitus treatment. In addition to glucose-lowering effects, emerging data, from clinical studies and their animal models, suggest that DPP-4i could display anti-inflammatory and immunomodulatory effects as well, but the molecular and immunological mechanisms of these actions are insufficiently investigated. This review focuses on the modulatory activity of DPP-4i in the immune system and the possible application of DPP-4i in other immune-related diseases in patients with or without diabetes.